1. ¹Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, USA
2. ²Department of Microbiology, University of Virginia Health System, Charlottesville, VA, USA

Correspondence: Dr TP Bender, Department of Microbiology, University of Virginia Health System, PO Box 800734, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0734, USA. E-mail: tpb3e@virginia.edu

Received 15 March 2005; Revised 21 October 2005; Accepted 28 November 2005; Published online 9 January 2006.

Abstract

The Myb proto-oncogene encodes a transcription factor (c-Myb) that is essential for normal hematopoiesis and is thought to regulate hematopoietic cell proliferation and differentiation by regulating expression of specific target genes. We identify the mouse erythroid-specific carbonic anhydrase I promoter (CAIe) as a target of c-Myb activity and demonstrate that Myb activity is critical for carbonic anhydrase I (CAI) expression in C19 MEL cells. CAI expression is downregulated when MEL cells differentiate in response to MEnT or treatment with N, N-hexamethylene bisacetamide (HMBA). Coexpression of GATA-1 with c-Myb results in synergistic activation of transcription from the CAIe promoter and both transcription factors interact with the CAIe promoter in vivo. We identify a novel 20 bp sequence in the CAIe promoter that is sufficient to mediate synergistic activation of the CAIe promoter by c-Myb and GATA-1. c-Myb and GATA-1 interact with this DNA sequence suggesting that c-Myb and GATA-1 may be contained in a complex that interacts with this region of the CAIe promoter. Forced expression of CAI delayed HMBA-induced differentiation of MEL cells and maintained them in a proliferating state. These data strongly suggest that CAI is a c-Myb target and is involved in regulating MEL cell proliferation and differentiation.